Glutathione
Description
Glutathione [L-y-glutamyl-L-cysteinyl-glycine, (GSH)] is a naturally occurring, small protein or peptide. It contains sulfur. It is formed by linking these 3 amino acids together: glutamic acid, cysteine and glycine.
Initially, glutathione was only associated with amino acid transportation across cell membranes. Current interest concerns its role as an antioxidant, possibly powerful enough to return malignant cells to healthy cells.
Glutathione works closely with cysteine and selenium.
Nutritional supplementation is often in the form of N-acetylcysteine (NAC), the precursor to glutathione.
Method of Action
Glutathione has several roles in the body:
Amino acid transportation
Anticarcinogenic
Antioxidation
Detoxification (especially heavy minerals)
Immune system
Mucolytic
Glutathione is highly soluble in water and 80% of an oral dose reaches the bloodstream within 3 hours.
Anticarcinogenic
Glutathione plays a role at several levels of the free-radical oxidation process. It provides cancer protection by destroying highly carcinogenic epoxides and peroxides.
It may also be beneficial in liver cancer. Other levels may be dealt with under the section on antioxidants.
Antioxidation
Glutathione is a key antioxidant factor. Not only does it perform free radical scavenging by itself but restores oxidized vitamin C and vitamin E, allowing them to function again.
Glutathione also combines with a selenium-containing enzyme as glutathione peroxidase.
Detoxification
Glutathione is useful against alcohol abuse, although it may be best-known for detoxifying heavy metals such as: cadmium, lead and mercury.
Immune system
Besides the detoxification processes already dealt with, glutathione improves the ability of the immune system's ability to destroy bacteria and remove "debris". Special white blood cells, called phagocytes, function better when well-nourished with glutathione.
Perhaps the ultimate test of immune enhancement, is in the elderly. Aged cells have glutathione levels 20 - 30% lower than young cells. Research efforts are under way to see if aged cells can absorb glutathione from oral supplementation, thereby restoring youthful cells.
Mucolytic
N-acetyl cysteine was demonstrated to have mucolytic properties in 1963. This had great potential in chronic lung diseases as it liquefies mucus.
Therapeutic Approaches
Glutathione (GSH) is being investigated in diverse areas:
Blood glutathione is a sensitive marker of oxidative stress, which may be monitored during illness.
Acute respiratory distress syndrome
Aging
AIDS
Alzheimer's
Cancer (e.g. breast, lung, prostate)
Liver disease
Lung disease
Parkinson's
Toxicology
Potential indications for GSH modulation are numerous.
Toxicity Factors
NAC is noted for detoxification and has been used for more than 30 years to treat overdoses of acetaminophen.
Dosages range from 200 mgs to over 1,800 mgs daily.
General dosages as an antioxidant are between 250 and 1,200 mgs daily, either in one dose, or divided doses.
Most studies are done, taking NAC in isolation. Complimentary vitamins (C and E) play a role in the metabolism and regeneration of glutathione.
NAC has been sold by health food stores for decades, so no alarming toxicity has been reported.
At high oral doses the following effects have been reported: diarrhea, nausea, vomiting.
References
Bounous, G. & Gold, P.: The biological activity of undenatured dietary whey proteins: role of glutathione. Clin. Invest. Med. 1991,14(4): 296-305.
Bray, T.M. & Taylor, C.G.: Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochem. Phar, 1994, 47(12): 2,113-2,123.
Ceballos-Picot, I. et al: Glutathione antioxidant system as a marker of oxidative stress in chronic renal failure. Free Radical Biol. Med. 1996, 21(6): 845-853.
Dorge, W. et al., Abnormal redox regulation in HIV infection and other immunodeficiency diseases. In: Pasquier et al., (eds) "Oxidative Stress, Cell Activation and Viral Infection". Birkhauser Verlag, Basel. 1994.
Eck, H.P. et al., Plasma glutamate levels, lymphocyte reactivity and death rate in patients with bronchial carcinoma. J. Cancer Res. Clin. Oncology, 1989,115:571-574.
Flanagan, R.J. & Meredith, T.J. : Use of N-acetylcysteine in clinical toxicology. Am. J. Med. 1988, 91 (Supp C):131S-139S.
Gissen, A.S. : N-Acetyl Cysteine. Nutritional News, June, 1994.
Kennedy, R.S. et al., The use of whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I - II clinical study. Anticancer Research, 1995, 15: 2,643-2,650.
Lomaestro, B.M. & Malone, M. : Glutathione in health and disease: pharmacotherapeutic issues. Ann. Pharmacother. 1995, 12: 1,263-1,273.
Meister, A. & Anderson, M.E.: Glutathione. Ann. Rev. Biochem. 1983, 52: 711-760.
Mitchell, J.R. et al., Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 1973, 187: 211-217.
Nijhoff, W.A. et al: Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferase in humans. Carcinogenesis, 1995, 16(9): 2,125-2,128.
Richie, J.P. : The role of glutathione in aging and cancer.
Ripple, M.O. et al., Prooxidant-antioxidant shift induced by androgen treatment of human prostate carcinoma cells. J. Ntnl. Cancer Inst. 1997, 89(1): 40-48.
Sies H. & Wendel, A. : Functions of Glutathione. Springer Verlag, NY, 1978.
Tessier, F. et al: Selenium and training effects on the glutathione system and aerobic performance. Med. Sci. Sports Ex. 1995, 27(3): 390-396.
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